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KMID : 0880420220230010101
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Korean Journal of Radiology
2022 Volume.23 No. 1 p.101 ~ p.111
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Whole Exome Sequencing in Patients with Phenotypically Associated Familial Intracranial Aneurysm
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Song Yun-Sun
Lee Jong-Keuk
Lee Jin-Ok
Kwon Bo-Seong
Seo Eul-Ju
Suh Dae-Chul
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Abstract
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Objective: Familial intracranial aneurysms (FIAs) are found in approximately 6%?20% of patients with intracranial aneurysms (IAs), suggesting that genetic predisposition likely plays a role in its pathogenesis. The aim of this study was to identify possible IA-associated variants using whole exome sequencing (WES) in selected Korean families with FIA.
Materials and Methods: Among the 26 families in our institutional database with two or more IA-affected first-degree relatives, three families that were genetically enriched (multiple, early onset, or common site involvement within the families) for IA were selected for WES. Filtering strategies, including a family-based approach and knowledge-based prioritization, were applied to derive possible IA-associated variants from the families. A chromosomal microarray was performed to detect relatively large chromosomal abnormalities.
Results: Thirteen individuals from the three families were sequenced, of whom seven had IAs. We noted three rare, potentially deleterious variants (PLOD3 c.1315G>A, NTM c.968C>T, and CHST14 c.58C>T), which are the most promising candidates among the 11 potential IA-associated variants considering gene-phenotype relationships, gene function, co-segregation, and variant pathogenicity. Microarray analysis did not reveal any significant copy number variants in the families.
Conclusion: Using WES, we found that rare, potentially deleterious variants in PLOD3, NTM, and CHST14 genes are likely responsible for the subsets of FIAs in a cohort of Korean families.
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KEYWORD
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Whole exome sequencing, Genetics, Familial intracranial aneurysm
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